Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug.

Abstract

About a quarter of patients with severe aplastic anemia remain pancytopenic despite immunosuppressive therapy. We have previously demonstrated that eltrombopag has efficacy in this setting with 44% (11/25) of patients having clinically significant hematologic responses. We now report safety and efficacy data on a further 18 patients and long-term follow-up on the entire cohort of 43 patients. The overall response rate was 17 of 43 patients (40%) at 3 to 4 months, including tri- and bilineage responses. The majority of patients who remained on eltrombopag in an extension study (14/17) continued to show improvement, and 7 eventually had significant increases in neutrophil, red cell, and platelet lineages. Five patients with robust near-normalization of blood counts had drug discontinued at a median of 28.5 months after entry (range, 9-37 months), and all maintained stable counts a median of 13 months (range, 1-15 months) off eltrombopag. Eight patients, including 6 nonresponders and 2 responders, developed new cytogenetic abnormalities on eltrombopag, including 5 with chromosome 7 loss or partial deletion. None evolved to acute myeloid leukemia to date. Eltrombopag is efficacious in a subset of patients with aplastic anemia refractory to immunosuppressive therapy, with frequent multilineage responses and maintenance of normalized hematopoiesis off treatment. This study is registered at www.clinicaltrials.gov as #NCT00922883.

• Authors: Ronan Desmond, Danielle M Townsley, Bogdan Dumitriu, Matthew J Olnes, Phillip Scheinberg, Margaret Bevans, Ankur R Parikh, Kinneret Broder, Katherine R Calvo, Colin O Wu, Neal S Young, Cynthia E Dunbar
• Journal: Blood (Blood) Vol. 123 Issue 12 Pg. 1818-25 (Mar 20 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24345753 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Benzoates
• Hematologic Agents
• Hydrazines
• Immunosuppressive Agents
• Pyrazoles
• Receptors, Thrombopoietin
• MPL protein, human
• eltrombopag

Topics

• Adolescent
• Adult
• Aged
• Anemia, Aplastic (blood, drug therapy, genetics)
• Benzoates (administration & dosage, adverse effects, therapeutic use)
• Bone Marrow (drug effects, pathology)
• Clonal Evolution (drug effects, genetics)
• Female
• Hematologic Agents (administration & dosage, adverse effects, therapeutic use)
• Hematopoiesis (drug effects)
• Hematopoietic Stem Cells (drug effects)
• Humans
• Hydrazines (administration & dosage, adverse effects, therapeutic use)
• Immunosuppressive Agents (therapeutic use)
• Male
• Middle Aged
• Pyrazoles (administration & dosage, adverse effects, therapeutic use)
• Receptors, Thrombopoietin (agonists)
• Young Adult